In vitro activity: Didanosine induces cytoplasmic lipid droplet accumulations, increases lactate production and decreases activities of COX (complex IV) and SDH (part of complex II) in cultured human muscle cells. Didanosine is converted to its active moiety, dideoxyadenosine-5'-triphosphate (ddATP), which inhibits HIV reverse transcriptase and terminates viral DNA growth in the target cell for HIV. Didanosine induces dose-dependent decreases in neurite number, length of the longest neurite in each neuron, and total neurite length per neuron in dissociated DRG cell cultures with 3 days treatment. Didanosine induces a neurite retraction or neurite loss in a dose-dependent manner in dissociated DRG neurons, suggesting that Didanosine may partially contribute to developing peripheral neuropathy. Didanosine potentiates the mutagenicity of Zidovudine in the thymidine kinase (TK) gene of cultured human TK6 lymphoblastoid cells. Didanosine combined with Zidovudine causes a significant increase in micronucleated PCEs and induces a significant increase in Tk mutants, which is associated with loss of the wild-type Tk+ allele. Didanosine depletes mitochondrial DNA (mtDNA) in cultured hepatocytes, this mtDNA depletion is associated with an increased in vitro production of lactate.